Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “CANTHARIDES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1980

Comparison of cefotaxime and moxalactam pharmacokinetics and tissue levels.

The pharmacokinetics of cefotaxime and moxalactam were compared in six healthy male volunteers aftr the administration of 1-g doses intravenously. Penetration of the compounds into tissue fluid was studied in cantharides-induced blisters. Both serum and tissue fluid levels of moxalactam were higher than those of cefotaxime. The elimination half-life of cefotaxime was 1.2 h, and that of moxalactam was 2.85 h. On the average, 50.5% of cefotaxime and 87.5% of moxalactam were recovered in the urine in 24 h.

Adult↗
PubMed1981

Comparison of ceftazidime and cefamandole pharmacokinetics and blister fluid concentrations.

Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The concentration of ceftazidime in serum at 0.25 h after intravenous injection was 83.3 micrograms/ml. The serum half-lives for the respective drugs were 1.8 and 0.8 h. The mean apparent volume of distribution of ceftazidime (13.6 liters) was greater than that of cefamandole (9.8 liters). Plasma clearance was 111 ml/min for ceftazidime and 216 ml/min for cefamandole. The maximum blister fluid concentration of ceftazidime was 45.9 micrograms/ml, and that of cefamandole was 22.1 micrograms/ml. The relative availability of each drug in blister fluid compared with serum was similar.

Adult↗
PubMed1982

Pharmacokinetics and tissue penetration of azthreonam.

Six healthy male volunteers received 1 g of azthreonam each as an intravenous injection. Serial blood and cantharides-induced blister fluid samples were taken over the next 8 h. Urine samples were collected over 24 h. The concentration of azthreonam in serum was about 50 micrograms/ml at 0.5 h after injection and fell to 2 to 3 micrograms/ml at 8 h; the serum half-life was 1.93 h, and the volume of distribution was equivalent to 12% of the mean body weight. The plasma clearance was 89.0 ml/min, 73.7% of the dose being recovered in the urine within 24 h. Azthreonam rapidly penetrated blister fluid, reaching a maximum of 25.4 micrograms/ml at 1.8 h after administration.

Adult↗
PubMed1987

Cefodizime in serum and skin blister fluid after single intravenous and intramuscular doses in healthy volunteers.

In gonorrhea therapy, cephalosporins are conventionally administered by intramuscular (i.m.) injection, which rather frequently leads to local side effects. To investigate whether the well-tolerated intravenous (i.v.) injection of cephalosporins may be of comparable gonocidal effect, levels of cefodizime, a new broad-spectrum cephalosporin, in serum and tissue fluid (suction blister and cantharides blister fluid) were determined in six healthy men. Single doses of 1 g of cefodizime were injected i.v. and i.m. according to a randomized crossover design. On i.m. injection the drug was completely bioavailable, and the peak concentration in serum was 75 +/- 8 micrograms/ml. The terminal half-life of serum levels was 2.4 h. Cefodizime concentrations in the blister fluids increased for 1.5 to 3 h after the i.v. dose and for at least 3 h on i.m. administration. The concentrations of non-protein-bound cefodizime in blister fluid already exceeded the MIC for 90% of Neisseria gonorrhoeae strains 10 min after i.v. injection and 20 to 30 min after the i.m. dose. At 6 h after each dose, active concentrations were still present in serum. The results suggest that cefodizime administered i.v. and i.m. has equivalent high cure rates in uncomplicated gonorrhea. This hypothesis should be tested further by a controlled clinical trial. If equivalent, i.v. administration excels because it is better tolerated locally.

Adult↗
PubMed1990

Multiple-dose pharmacokinetics of ofloxacin in serum, saliva, and skin blister fluid of healthy volunteers.

The pharmacokinetics of ofloxacin were determined in six healthy volunteers after oral administration of 200 mg twice daily for 3.5 days. To study the pharmacokinetic behavior at the target site in bacterial infection of the skin, drug concentrations were determined in suction blister fluid (SBF) and cantharides blister fluid (CBF), as well as in serum and saliva. Ofloxacin was measured by a high-performance liquid chromatographic assay. Ofloxacin concentrations in saliva amounted to 61 +/- 3% of levels in serum. After the final dose, ofloxacin concentrations in blister fluid and serum declined in parallel. Terminal half-lives of ofloxacin in blister fluids (SBF, 7.0 h; CBF, 6.3 h) were in accordance with serum half-life (6.6 h). Favorable penetration into the skin is suggested by high area under the concentration-time curve ratios for blister fluid and serum (CBF, 1.1; SBF, 1.3). During repeated ofloxacin intake, drug levels in SBF and CBF at 12 h amounted to 0.94 and 1.10 micrograms/ml. Thus, ofloxacin levels in the skin are well above the MIC for 90% of strains tested for, e.g., Staphylococcus aureus, Staphylococcus epidermidis, Neisseria gonorrhoeae, and various members of the family Enterobacteriaceae. This should also hold true with respect to other tissues.

Adult↗
PubMed1992

Pharmacokinetics and inflammatory fluid penetration of sparfloxacin.

A single 400-mg oral dose of sparfloxacin was given to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 52 h. The mean peak concentration in plasma of 1.6 micrograms/ml was attained at a mean time of 2.7 h postdose. The mean peak concentration in inflammatory fluid of 1.3 micrograms/ml was attained at a mean time of 5 h postdose. The mean elimination half-life in plasma was 17.6 h, and that in inflammatory fluid was 19.7 h. The overall penetration into inflammatory fluid was 117%. Urinary recovery within the first 52 h postdose was 8.8% of the administered dose. Our results indicate that a once-daily dosage of sparfloxacin should be adequate to treat systemic infections caused by most common bacterial pathogens.

Administration, Oral↗
PubMed1994

Pharmacokinetics and distribution in tissue of FK-037, a new parenteral cephalosporin.

A single 1-g or 2-g intravenous dose of the cephalosporin FK-037 was given over 30 min in a cross-over-designed study, to each of six healthy male volunteers, and the concentrations of the drug were measured in plasma and cantharides-induced blister fluid over the subsequent 12 h. Urine was collected over 24 h. After a washout period of 6 weeks, during which the blisters healed, the study was repeated at the other dose level. Following the 1-g dose, the mean peak concentration in plasma was 83.8 micrograms/ml, and after the 2-g dose it was 142.6 micrograms/ml. The mean peak concentrations in the inflammatory fluid were 37.9 and 63.3 micrograms/ml, respectively. The mean elimination half-lives from plasma and inflammatory fluid were 2.0 and 2.5 h, respectively, after 1 g and 2.0 h and 3.7 h, respectively, after 2 g. The amounts of penetration into inflammatory fluid (as assessed by ratios of areas under the concentration-time curves) were 109.9 and 110.5% following doses of 1 and 2 g, respectively. The proportions of the administered drug recovered in the urine by 24 h were 87.6 and 85.7%, respectively. Our results indicate that FK-037 should prove to be efficacious in the treatment of a wide range of systemic infections.

Adult↗
PubMed1995

Pharmacokinetics and tissue penetration of the new fluoroquinolone grepafloxacin.

A single 400-mg oral dose of grepafloxacin (OPC-17116) was given to each of six healthy male volunteers, and the concentrations of the drug in plasma, cantharides-induced inflammatory fluid, and urine were measured over the subsequent 12 h. The mean peak concentration in plasma of 1.5 micrograms/ml was attained at a mean time of 2.0 h postdose. The mean peak concentration in inflammatory fluid of 1.1 micrograms/ml was attained at a mean time of 4.8 h postdose. The mean elimination half-life in plasma was 5.2 h, and that in inflammatory fluid was 12.7 h. The overall penetration into inflammatory fluid was 180.6% (or 133% if one aberrant result from one volunteer is excluded). Recovery of the drug in urine during the first 24 h postdose was 8.3% of the administered dose. Our results indicate that a once- or twice-daily dosage of grepafloxacin should be adequate to treat systemic infections caused by most bacterial pathogens.

Adult↗
PubMed1996

Pharmacokinetics of cefetamet in plasma and skin blister fluid.

Cefetamet pivoxil is an oral cephalosporin with enhanced affinity for the target penicillin-binding proteins 1 and 3 and an increased stability to beta-lactamases compared with older cephalosporins, such as cefalexin or cefaclor. The pharmacokinetics of cefetamet pivoxil was determined after the seventh and final dose of 500 mg of cefetamet pivoxil in eight healthy volunteers. Concentrations in plasma and cantharidin-induced skin blister fluid were determined by a high-performance liquid chromatography method. In addition, protein binding was assessed. Cmax was 4.8 +/- 1.7 micrograms/ml in skin blister fluid and 5.1 +/- 2.1 micrograms/ml in plasma. Tmax was delayed in skin blister fluid compared with plasma (3.9 +/- 1 versus 2.8 +/- 0.8 h; P < 0.001), and t1/2 was longer in skin blister fluid than in plasma (3.1 +/- 0.5 versus 2.3 +/- 0.3; P < 0.005). The mean percent penetration into cantharide blister fluid was 129% +/- 24% when measured as total drug and 149% +/- 28% when measured as free drug (P < 0.001). These data suggest that cefetamet has an excellent penetration into inflammatory interstitial fluid.

Adult↗
PubMed1996

Pharmacokinetics and penetration into inflammatory fluid of trovafloxacin (CP-99,219).

A single 200-mg oral dose of trovafloxacin (CP-99,219) was given to each of eight healthy male volunteers, and the concentrations of the drug were measured in plasma, cantharides-induced inflammatory fluid, and urine over the subsequent 36 h. The mean maximum concentration observed in plasma was 2.9 micrograms/ml at a mean time of 0.75 h postdose. The mean maximum concentration observed in inflammatory fluid was 1.2 micrograms/ml at 4.0 h postdose. The mean elimination half-life in plasma was 7.8 h. The overall penetration into inflammatory fluid was 64%, as assessed by determining the ratio of the area under the concentration-time curves. Recovery of the dose in urine within the first 36 h postdose was 5.0% of the administered dose. Our results indicate that trovafloxacin, at a dosage of 200 mg once or twice daily, should be adequate for the treatment of systemic infections caused by most common bacterial pathogens.

Adolescent↗
PubMed1999

Penetration of moxifloxacin into peripheral compartments in humans.

To characterize the penetration of moxifloxacin (BAY 12-8039) into peripheral target sites, the present study aimed at measuring unbound moxifloxacin concentrations in the interstitial space fluid by means of microdialysis, an innovative clinical sampling technique. In addition, moxifloxacin concentrations were measured in cantharides-induced skin blisters, saliva, and capillary plasma and compared to total- and free-drug concentrations in venous plasma. For this purpose, 12 healthy volunteers received moxifloxacin in an open randomized crossover fashion either as a single oral dose of 400 mg or as a single intravenous infusion of 400 mg over 60 min. An almost-complete equilibration of the free unbound plasma fraction of moxifloxacin with the interstitial space fluid was observed, with mean area under the concentration-time curve (AUC)(interstitial fluid)/AUC(total-plasma) ratios ranging from 0.38 to 0.55 and mean AUC(interstitial fluid)/AUC(free-plasma) ratios ranging from 0.81 to 0.86. The skin blister concentration/plasma concentration ratio reached values above 1.5 after 24 h, indicating a preferential penetration of moxifloxacin into inflamed lesions. The moxifloxacin concentrations in saliva and capillary blood were similar to the corresponding levels in plasma. Our data show that moxifloxacin concentrations attained in the interstitial space fluid in humans and in skin blister fluid following single doses of 400 mg exceed the values for the MIC at which 90% of isolates are inhibited for most clinically relevant bacterial strains, notably including penicillin-resistant Streptococcus pneumoniae. These findings support the use of moxifloxacin for the treatment of soft tissue and respiratory tract infections in humans.

4-Quinolones↗
PubMed2005

Pharmacokinetics of oritavancin in plasma and skin blister fluid following administration of a 200-milligram dose for 3 days or a single 800-milligram dose.

Oritavancin is a novel glycopeptide currently being developed for the treatment of complicated skin and skin structure infections (cSSSI), including those caused by multidrug resistant gram-positive pathogens. The disposition of oritavancin in skin structures was investigated using a cantharide-induced blister fluid model. Seventeen healthy male subjects received oritavancin, but only 16 subjects were evaluated after one subject discontinued study drug. Each subject (eight per dose group) received 200 mg of oritavancin once a day for 3 days (group A) or 800 mg as one single dose (group B). Group A plasma samples and exudates from blister fluid were collected on days 3, 4, 7, 9, and 12 and on days 3, 4, 7, and 9, respectively. Group B samples and exudates were collected on days 1, 2, 5, 7, and 10 and on days 1, 2, 5, and 7, respectively. Drug concentrations were determined using a liquid chromatography-tandem mass spectrometry assay and, subsequently, pharmacokinetic analysis was performed. Differences between treatment groups in ratios for area under the concentration-time curve for blister fluid and plasma (AUC(blister fluid)/AUC(plasma) ratios) were evaluated using a t test (alpha = 0.05). Mean maximum concentration of drug in plasma or blister fluid was approximately 8-fold and 11-fold higher in plasma than in blister fluid following the 200- or 800-mg doses of oritavancin, respectively. Mean AUC(blister fluid)/AUC(plasma) ratios at 24 h were 0.190 (standard deviation [SD], 0.052) and 0.182 (SD, 0.062) for groups A and B, respectively (P = 0.791). To place these results in a clinical context, mean drug concentrations in blister fluid exceed the oritavancin MIC at which 90% of strains are inhibited of Staphylococcus aureus (2 microg/ml) by approximately 2- to 5.5-fold at 12 h and 1.5- to 3-fold at 24 h following administration of both dosing regimens. These results support the potential use of oritavancin for the treatment of cSSSI.

Adult↗
PubMed1998

Modulation of the Ca2+-activated K+ current sIAHP by a phosphatase-kinase balance under basal conditions in rat CA1 pyramidal neurons.

The slow Ca2+-activated K+ current, sIAHP, underlying spike frequency adaptation, was recorded with the whole cell patch-clamp technique in CA1 pyramidal neurons in rat hippocampal slices. Inhibitors of serine/threonine protein phosphatases (microcystin, calyculin A, cantharidic acid) caused a gradual decrease of sIAHP amplitude, suggesting the presence of a basal phosphorylation-dephosphorylation turnover regulating sIAHP. Because selective calcineurin (PP-2B) inhibitors did not affect the amplitude of sIAHP, protein phosphatase 1 (PP-1) or 2A (PP-2A) are most likely involved in the basal regulation of this current. The ATP analogue, ATP-gamma-S, caused a gradual decrease in the sIAHP amplitude, supporting a role of protein phosphorylation in the basal modulation of sIAHP. When the protein kinase A (PKA) inhibitor adenosine-3', 5'-monophosphorothioate, Rp-isomer (Rp-cAMPS) was coapplied with the phosphatase inhibitor microcystin, it prevented the decrease in the sIAHP amplitude that was observed when microcystin alone was applied. Furthermore, inhibition of PKA by Rp-cAMPS led to an increase in the sIAHP amplitude. Finally, an adenylyl cyclase inhibitor (SQ22, 536) and adenosine 3',5'-cyclic monophosphate-specific type IV phosphodiesterase inhibitors (Ro 20-1724 and rolipram) led to an increase or a decrease in the sIAHP amplitude, respectively. These findings suggest that a balance between basally active PKA and a phosphatase (PP-1 or PP-2A) is responsible for the tonic modulation of sIAHP, resulting in a continuous modulation of excitability and firing properties of hippocampal pyramidal neurons.

Adenylyl Cyclases↗
PubMed2001

PP1 inhibitors depolarize Hermissenda photoreceptors and reduce K+ currents.

Previous research indicates that activation of protein kinase C (PKC) plays a critical role in the induction and maintenance of memory-related changes in neural excitability of Type B photoreceptors in the eyes of nudibranch mollusk Hermissenda crassicornis (H.c.). The enhanced excitability of B cells is due in part to PKC-mediated reduction in somatic K+ currents. Here we examined the effects of protein phosphatase inhibitors on Type B photoreceptor excitability and K+ currents to determine the role(s) of protein phosphatases on memory formation in Hermissenda. Using electrophysiological and pharmacological methods, we found that the PP1 inhibitors calyculin A and inhibitor-2 depolarized Type B photoreceptors by 20-30 mV. A broad-spectrum kinase inhibitor, H7, blocked this effect. The depolarization induced by PP1 inhibition occluded that produced by an in vitro associative conditioning procedure. Calyculin and inhibitor-2 reduced the same B cell K+ currents (I(A) and I(delayed)) that are reduced by in vitro and behavioral conditioning. H7 blocked the reductions. Cantharidic acid (PP2A inhibitor) and cyclosporin (PP2B inhibitor) had negligible effects on B cell resting membrane potential, K+ currents, and in vitro conditioning-produced cumulative depolarization of B cells. These results suggest that the functional activity of K+ channels in B cells is sustained by basal activity of PP1. Inhibiting PP1 appears to allow one or more constitutively active kinase(s) to reduce K+ channel activity and thus mimic the effects of conditioning. Our results suggest that PP1 may oppose and/or constrain the extent of learning-produced changes in B cell excitability.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Rapid aggressive soft-tissue necrosis after beetle bite can be treated by radical necrectomy and vacuum suction-assisted closure.

BACKGROUND: The substance cantharidin, which is produced by a type of beetle, rapidly penetrates the epidermis and can cause severe toxicities such as skin necrosis. Optimal treatment for necrotic beetle bites has not been well defined. Conservative management has been advocated but the hospital stays are long and long-term morbidity may result, especially in multimorbid patients. OBJECTIVE: The value of aggressive surgical management of such necrotizing diseases using newly developed surgical tools is compared to the traditional more conservative approach. RESULTS: We present the case of a multimorbid 60-year-old man with a rapidly progressive necrosis of the medial thigh (measuring 30 X 15 cm), acquired during a stay in Western Africa after being bitten by a beetle of the species Cantharide. The patient was treated with radical surgical debridement and continuous elimination of the wound fluid by permanent computer-controlled negative pressure with a vacuum-assisted wound-closure device. This led to the sudden relief of both local and systemic symptoms and allowed extremely early wound closure. CONCLUSIONS: Comparing literature data with the course of this combined treatment, we strongly suggest an early aggressive management with complete radical excision of necrotic tissue, conditioning of the wound bed by temporary suction-assisted vacuum closure and subsequent skin grafting with continued vacuum application. This treatment leads to immediate relief of pain and enhanced healing of this lesion even in the condition of immunosuppression in the elderly.

Animals↗
PubMed1985

Pharmacokinetics and tissue penetration of temocillin.

The pharmacokinetics of intravenous (bolus) temocillin 1 g were studied in 6 healthy male volunteers, and a cantharides blister method was used to estimate tissue penetration of the antibiotic. The mean elimination half-life was 4.5 hours. Temocillin penetrated blister fluid rapidly and reached concentrations of about 50% of those in serum by 2 to 3 hours after administration. Over an 8-hour period, the serum and blister fluid concentrations exceeded the MIC90 of susceptible bacteria by 2-fold or greater, suggesting that twice or even once daily dosing with temocillin may be sufficient.

Blister↗
PubMed1987

New spiroplasmas from insects and flowers: isolation, ecology, and host association.

Eight spiroplasma strains from insects and one from spring flowers failed to react with antisera specific for any of the 11 described spiroplasma groups, with sera directed against spiroplasma Group I subgroups, or with sera directed against two unnumbered groups previously reported to occur in tabanid flies. Strains, all from Maryland, were isolated from the hemolymph of the spotted cucumber beetle Diabrotica undecimpunctata and the lampyrid beetle Ellychnia corrusca, and the guts of the cantharid beetles Cantharis bilineatus and C. carolinus. Other strains were obtained from a tabanid fly, Tabanus gladiator and from the firefly Photuris pennsylvanica in Maryland and from the mosquito Culex tritaeniorhynchus in Taiwan. An isolate from pooled Cicadulina bipunctella leafhoppers in Syria apparently represented a unique group. A single isolate from spring flowers in Oklahoma also appeared to be unrelated to existing groups or subgroups. One-way deformation tests using sera prepared against known beetle and tabanid spiroplasmas showed each of the above strains to be unique. Although these results strongly indicate that the nine strains studied are representatives of unique new spiroplasma groups, the formal designation of new groups awaits fulfillment of recently proposed criteria.

Animals↗
PubMed1977

[Diminution of the percentage of mononucleated phagocytes in patients with breast cancer].

Phagocytic activity of macrophages obtained directly from blisters induced by cantharide was studied in 19 normal women and 21 patients with untreated operable carcinoma of the breast. The percentage of mononuclear phagocytes from cancer patients was significantly decreased as compared to the percentage from control Women. The reasons for this phagocyte inertia in these patients remain to be determined.

Adult↗